With neural tube defect (NTD) rates of up to 106 cases per 10,000 births (20:10,000 world average), Guatemala's NTD prevalence is among the highest in the world (Cifuentes 2002). As the predisposition to and development of NTDs is complex, with both environmental and hereditary factors implicated, it is hypothesized that the high prevalence of NTDs in Guatemala is due to interactions between an underlying genetic predisposition in association with a common environmental exposure, fumonisin. The NTD Collaborative Study's whole genome single nucleotide polymorphism (SNP) screen will be used as a starting point for linkage analysis and potential candidate gene investigation. To compliment this linkage analysis, the transcriptome of fumonisin exposed C. elegans will also be characterized through the use of microarray technology. Using the candidate genes detected in the whole genom e SNP screen and C. elegans studies, 100 simplex Guatemalan pedigrees will then be evaluated using fam ily-based association methods. Fumonisin exposure will also be looked at as a potential environmental risk factor using statistical methods to test for gene-environment interactions.